Time-restricted feeding alleviates metabolic implications of circadian disruption by regulating gut hormone release and brown fat activation

Individuals with rotating and night shift work are highly susceptible to developing metabolic disorders such as obesity and diabetes. This is primarily attributed to disruptions in the circadian rhythms caused by activities and irregular eating habits. Time-restricted feeding (tRF) limits the daily eating schedules and has been demonstrated to markedly improve several metabolic disorders. Although an intricate relationship exists between tRF and circadian rhythms, the underlying specific mechanism remains elusive. We used a sleep disruption device for activity interference and established a model of circadian rhythm disorder in mice with different genetic backgrounds. We found that circadian rhythm disruption led to abnormal hormone secretion in the gut and elevated insulin resistance. tRF improved metabolic abnormalities caused by circadian rhythm disruption, primarily by restoring the gut hormone secretion rhythm and activating brown fat thermogenesis. The crucial function of brown fat in tRF was confirmed using a mouse model with brown fat removal. We demonstrated that chenodeoxycholic acid (CDCA) effectively improved circadian rhythm disruption-induced metabolic disorders by restoring brown fat activation. Our findings demonstrate the potential benefits of CDCA in reversing metabolic disadvantages associated with irregular circadian rhythms.